Eliseo Guallar
Eliseo Guallar
Scroll
Chair and Professor of the Department of Epidemiology
-
Professional overview
-
Dr. Guallar is an epidemiologist whose research is focused on the study of cardiovascular disease epidemiology and prevention, with an emphasis on evaluating the role of environmental and nutritional exposures in the development of cardiovascular disease. This research has made critically important and novel contributions to our understanding of risk factors for chronic disease both in the US and globally. He has published seminal articles and is a leading figure in an emerging field highlighting the risks of exposure to levels of metals previously considered safe for cardiovascular health. In addition to his work in toxic metals, Dr. Guallar has made important contributions to understanding the effects of certain micronutrients and vitamin supplements on cardiovascular disease risk and outcomes. Publications in this area were influential in changing consumer habits and attitudes towards these products. Much of this research has been funded by the National Institutes of Health, the Agency for Healthcare Research and Quality, the American Heart Association, the CDC, and other funders.
Dr. Guallar was the founding director of the Center for Clinical Epidemiology at the Samsung Medical Center and a lead investigator of the Kangbuk Samsung Cohort Study at the Kangbuk Samsung Hospital since its inception in 2010. Dr. Guallar has published over 500 research papers in peer-reviewed journals. He is also a Deputy Editor for Methods at the Annals of Internal Medicine and a past member and Chair of the Cancer, Heart, and Sleep Study Section at the National Institutes of Health.
Prior to teaching at NYU, Dr. Guallar was a Professor of Epidemiology and Medicine at the Johns Hopkins University Bloomberg School of Public Health and a core faculty member of the Welch Center for Prevention, Epidemiology, and Clinical Research at Johns Hopkins. In the Department of Epidemiology, Dr. Guallar was the Director of the Environmental and Occupational Area of Concentration and the Co-Director of the PhD Program. Dr. Guallar was also an adjunct Professor at the Department of Clinical Research Design and Evaluation of the Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, in Seoul, Korea.
-
Education
-
Diploma of English, Spanish Official School of Languages at Zaragoza (Escuela Oficial de Idiomas de Zaragoza), Zaragoza, SpainMD, University of Zaragoza, Zaragoza, SpainMPH, University of Minnesota, Minneapolis, MNDrPH, Harvard University, Boston, MA
-
Honors and awards
-
Six Honor Calls in the MD Program, University of Zaragoza School of Medicine (1981)Fellow of Spain’s Program of Training of Graduate Research of the Ministry of Education and Science, University of Zaragoza (1988)Fulbright Scholar, sponsored by Spain’s Ministry of Health and Consumer Affairs (1989)Faculty Innovation Award, Johns Hopkins University Bloomberg School of Public Health (2001)Scientist Development Award, American Heart Association (2002)Fellow of the American Heart Association, Council on Epidemiology and Prevention (2013)Advising, Mentoring, and Teaching Recognition Award 2014 – 2015, Johns Hopkins University Bloomberg School of Public Health (2015)High Impact Research Icon, University of Malaya (2015)
-
Publications
Publications
Association of Eating and Sleeping Intervals With Weight Change Over Time: The Daily24 Cohort
AbstractZhao, D., Guallar, E., Woolf, T. B., Martin, L., Lehmann, H., Coughlin, J., Holzhauer, K., Goheer, A. A., McTigue, K. M., Lent, M. R., Hawkins, M., Clark, J. M., & Bennett, W. L. (n.d.).Publication year
2023Journal title
Journal of the American Heart AssociationVolume
12Issue
3AbstractBACKGROUND: We aim to evaluate the association between meal intervals and weight trajectory among adults from a clinical cohort. METHODS AND RESULTS: This is a multisite prospective cohort study of adults recruited from 3 health systems. Over the 6-month study period, 547 participants downloaded and used a mobile application to record the timing of meals and sleep for at least 1 day. We obtained information on weight and comorbidities at each outpatient visit from electronic health records for up to 10 years before until 10 months after baseline. We used mixed linear regression to model weight trajectories. Mean age was 51.1 (SD 15.0) years, and body mass index was 30.8 (SD 7.8) kg/m2; 77.9% were women, and 77.5% reported White race. Mean interval from first to last meal was 11.5 (2.3) hours and was not associated with weight change. The number of meals per day was positively associated with weight change. The average difference in annual weight change (95% CI) associated with an increase of 1 daily meal was 0.28 kg (0.02–0.53). CONCLUSIONS: Number of daily meals was positively associated with weight change over 6 years. Our findings did not support the use of time-restricted eating as a strategy for long-term weight loss in a general medical population.Association of single and joint metals with albuminuria and estimated glomerular filtration longitudinal change in middle-aged adults from Spain: The Aragon workers health study
AbstractGrau-Perez, M., Domingo-Relloso, A., Garcia-Barrera, T., Gomez-Ariza, J. L., Leon-Latre, M., Casasnovas, J. A., Moreno-Franco, B., Laclaustra, M., Guallar, E., Navas-Acien, A., Pastor-Barriuso, R., Redon, J., & Tellez-Plaza, M. (n.d.).Publication year
2023Journal title
Environmental PollutionVolume
318AbstractThe nephrotoxicity of low-chronic metal exposures is unclear, especially considering several metals simultaneously. We assessed the individual and joint association of metals with longitudinal change in renal endpoints in Aragon Workers Health Study participants with available measures of essential (cobalt [Co], copper [Cu], molybdenum [Mo] and zinc [Zn]) and non-essential (As, barium [Ba], Cd, chromium [Cr], antimony [Sb], titanium [Ti], uranium [U], vanadium [V] and tungsten [W]) urine metals and albumin-to-creatinine ratio (ACR) (N = 707) and estimated glomerular filtration rate (eGFR) (N = 1493) change. Median levels were 0.24, 7.0, 18.6, 295, 3.1, 1.9, 0.28, 1.16, 9.7, 0.66, 0.22 μg/g for Co, Cu, Mo, Zn, As, Ba, Cd, Cr, Sb, Ti, V and W, respectively, and 52.5 and 27.2 ng/g for Sb and U, respectively. In single metal analysis, higher As, Cr and W concentrations were associated with increasing ACR annual change. Higher Zn, As and Cr concentrations were associated with decreasing eGFR annual change. The shape of the longitudinal dose-responses, however, was compatible with a nephrotoxic role for all metals, both in ACR and eGFR models. In joint metal analysis, both higher mixtures of Cu–Zn–As–Ba–Ti–U–V–W and Co–Cd–Cr–Sb–V–W showed associations with increasing ACR and decreasing eGFR annual change. As and Cr were main drivers of the ACR change joint metal association. For the eGFR change joint metal association, while Zn and Cr were main drivers, other metals also contributed substantially. We identified potential interactions for As, Zn and W by other metals with ACR change, but not with eGFR change. Our findings support that Zn, As, Cr and W and suggestively other metals, are nephrotoxic at relatively low exposure levels. Metal exposure reduction and mitigation interventions may improve prevention and decrease the burden of renal disease in the population.Associations of urinary isoprostanes with measures of subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA)
AbstractWallace, R. L., Ogunmoroti, O., Zhao, D., Vaidya, D., Heravi, A., Guallar, E., Ndumele, C. E., Lima, J. A., Ouyang, P., Budoff, M. J., Allison, M., Thomas, I., Fashanu, O. E., Hoogeveen, R., Post, W. S., & Michos, E. D. (n.d.).Publication year
2023Journal title
Atherosclerosis PlusVolume
51Page(s)
13-21AbstractBackground: Urinary isoprostanes are markers of systemic oxidative stress, which is implicated in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC), thoracic aortic calcium (TAC) and carotid plaque are measure subclinical atherosclerosis and prognosticate ASCVD risk. We examined the associations between urinary isoprostane levels and measures of plaque prevalence, burden, incidence and progression across three vascular beds in a cohort from the Multi-Ethnic Study of Atherosclerosis. Methods: Urinary levels of 8-isoprostane and 2,3-dinor-8-F2-isoprostane were measured in 1089 participants (mean ± SD 62 ± 8 years, 48% women) at baseline. Participants underwent computed tomography for CAC and TAC, and duplex ultrasound for carotid plaque. TAC and CAC were reassessed at 2.4 and 10 years, respectively. Regression models were adjusted for CVD risk factors. Results: In adjusted models, there were no significant associations between isoprostane levels with CAC prevalence or progression. Highest versus lowest tertile of 8-isoprostane was associated with 28% lower prevalence of descending TAC at baseline [prevalence ratio (PR) 0.72 95% CI (0.56, 0.94)], while 1-SD higher 2,3-dinor-8-F2-isoprostane was associated with 96% higher incident ascending TAC at follow-up [Relative Risk 1.96 (1.24, 3.09)]. Highest versus lowest tertile of isoprostane measures were associated with 22% higher prevalence of carotid plaque [(PR 1.22 (1.04, 1.45)] and 14% difference [3,26] in greater extent of carotid plaque at baseline. Conclusions: Higher urinary isoprostanes were inconsistently associated with some measures of subclinical atherosclerosis by imaging. This suggests a limited role of urinary isoprostane levels as a prognostic marker for the development of ASCVD. Trial registration: The MESA cohort design is registered at clinicaltrials.gov as follows: https://clinicaltrials.gov/ct2/show/NCT00005487.Comparison Between Fimasartan Versus Other Angiotensin Receptor Blockers in Patients With Heart Failure After Acute Myocardial Infarction
AbstractKim, J., Kang, D., Kim, S. E., Park, H., Park, T. K., Lee, J. M., Yang, J. H., Song, Y. B., Choi, J. H., Choi, S. H., Gwon, H. C., Guallar, E., Cho, J., & Hahn, J. Y. (n.d.).Publication year
2023Journal title
Journal of Korean Medical ScienceVolume
38Issue
25AbstractBackgrounds: Fimasartan is the most recently developed, potent, and long-acting angiotensin II receptor blocker (ARB). However, data are limited regarding treatment effects of fimasartan in patients with heart failure. Methods: Between 2010 and 2016, patients who underwent coronary revascularization for myocardial infarction (MI) with heart failure and prescription of ARB at hospital discharge were enrolled from the Korean nationwide medical insurance data. Clinical outcomes were compared between patients receiving fimasartan and those receiving other ARBs (candesartan, valsartan, losartan, telmisartan, olmesartan, and irbesartan). The primary outcome was a composite of all-cause death, recurrent MI, hospitalization for heart failure, and stroke. Results: Of 2,802 eligible patients, fimasartan was prescribed to 124 patients (4.4%). During a median follow-up of 2.2 years (interquartile range, 1.0–3.9), 613 events of the primary outcome occurred. There was no significant difference in the primary outcome between patients receiving fimasartan and those receiving other ARBs (adjusted hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.46–1.45). Compared with patients receiving other ARBs, those receiving fimasartan had comparable incidence of all-cause death (adjusted HR, 0.70; 95% CI, 0.30–1.63), recurrent MI (adjusted HR, 1.28; 95% CI, 0.49–3.34), hospitalization for heart failure (adjusted HR, 0.70; 95% CI, 0.27–1.84), and stroke (adjusted HR, 0.59; 95% CI, 0.18–1.96). Conclusion: In this nationwide cohort, fimasartan, compared with other ARBs, had comparable treatment effects for a composite of all-cause death, recurrent MI, hospitalization for heart failure, and stroke in patients with heart failure after MI.Deleterious heteroplasmic mitochondrial mutations are associated with an increased risk of overall and cancer-specific mortality
AbstractHong, Y. S., Battle, S. L., Shi, W., Puiu, D., Pillalamarri, V., Xie, J., Pankratz, N., Lake, N. J., Lek, M., Rotter, J. I., Rich, S. S., Kooperberg, C., Reiner, A. P., Auer, P. L., Heard-Costa, N., Liu, C., Lai, M., Murabito, J. M., Levy, D., … Arking, D. E. (n.d.).Publication year
2023Journal title
Nature communicationsVolume
14Issue
1AbstractMitochondria carry their own circular genome and disruption of the mitochondrial genome is associated with various aging-related diseases. Unlike the nuclear genome, mitochondrial DNA (mtDNA) can be present at 1000 s to 10,000 s copies in somatic cells and variants may exist in a state of heteroplasmy, where only a fraction of the DNA molecules harbors a particular variant. We quantify mtDNA heteroplasmy in 194,871 participants in the UK Biobank and find that heteroplasmy is associated with a 1.5-fold increased risk of all-cause mortality. Additionally, we functionally characterize mtDNA single nucleotide variants (SNVs) using a constraint-based score, mitochondrial local constraint score sum (MSS) and find it associated with all-cause mortality, and with the prevalence and incidence of cancer and cancer-related mortality, particularly leukemia. These results indicate that mitochondria may have a functional role in certain cancers, and mitochondrial heteroplasmic SNVs may serve as a prognostic marker for cancer, especially for leukemia.Effect of Anemia on Physical Function and Physical Activity in CKD: The National Health and Nutrition Examination Survey, 1999-2016
AbstractFarag, Y. M., Blasco-Colmenares, E., Zhao, D., Sanon, M., Guallar, E., & Finkelstein, F. O. (n.d.).Publication year
2023Journal title
Kidney360Volume
4Issue
9Page(s)
E1212-E1222AbstractKey PointsIn a large sample representative of the US adult noninstitutionalized population, among participants with CKD stages 3-5, anemia was associated with a significantly lower level of physical activity.The presence of CKD and anemia showed a positive interaction on physical functioning outcomes. Among participants with CKD, physical functioning was worse in patients with anemia compared with those without anemia.BackgroundCKD is a major public health problem worldwide. Anemia, a frequent and treatable complication of CKD, is associated with decreased physical functioning and physical activity. The objective of this study was to evaluate the joint association of CKD and anemia with physical functioning and physical activity in a representative sample of the US population.MethodsCross-sectional study using the National Health and Nutrition Examination Survey (NHANES) 1999-2016 for physical functioning outcomes (N=33,300) and NHANES 2007-2016 for physical activity (N=22,933). The NHANES physical functioning questionnaire included 19 items. The NHANES physical activity questionnaire captured work-related, leisure-time, and sedentary activities. Higher physical functioning scores represent worse function. CKD was classified using Kidney Disease Outcomes Quality Initiative 2002 criteria, and anemia was defined using the World Health Organization criteria.ResultsThe adjusted mean differences (95% confidence interval) in overall physical functioning score comparing participants with anemia with those without anemia among participants with no CKD, CKD stages 1-2, and stages 3-5 were 0.5 (-0.1 to 1.0), 1.5 (0.2 to 2.8), and 3.6 (2.0 to 5.2). Anemia and CKD showed a supra-additive interaction for all physical functioning outcomes among participants in CKD stages 3-5. The prevalence of high physical activity was also lower in participants with anemia compared with those without anemia among participants in CKD stages 3-5 (adjusted prevalence ratio, 0.74; 95% confidence interval, 0.54 to 1.01).ConclusionsCKD and anemia were associated with impairments in physical functioning and reduced physical activity. For physical functioning outcomes, the combined presence of CKD and of anemia showed a stronger effect than what was expected from their independent effects.Long-Term Air Pollution Exposure and Mitochondrial DNA Copy Number: An Analysis of UK Biobank Data
Hong, Y. S., Battle, S. L., Puiu, D., Shi, W., Pankratz, N., Zhao, D., Arking, D. E., & Guallar, E. (n.d.). In Environmental health perspectives (1–).Publication year
2023Volume
131Issue
5Moderate-Intensity Statins Plus Ezetimibe vs. High-Intensity Statins After Coronary Revascularization: A Cohort Study
AbstractKim, J., Kang, D., Park, H., Kang, M., Choi, K. H., Park, T. K., Lee, J. M., Yang, J. H., Song, Y. B., Choi, J. H., Choi, S. H., Gwon, H. C., Guallar, E., Cho, J., & Hahn, J. Y. (n.d.).Publication year
2023Journal title
Cardiovascular Drugs and TherapyVolume
37Issue
1Page(s)
141-150AbstractPurpose: Whether moderate-intensity statins plus ezetimibe could be an alternative to high-intensity statins in patients with atherosclerotic cardiovascular disease is unclear. We compared the risk of adverse cardiovascular events in patients receiving moderate-intensity statins plus ezetimibe vs. high-intensity statins after a coronary revascularization procedure using data from a large cohort study. Method: Population-based cohort study using nationwide medical insurance data from Korea. Study participants (n = 20,070) underwent percutaneous coronary intervention or coronary artery bypass graft surgery between January 1, 2015, and December 31, 2016, and received moderate-intensity statins (atorvastatin 10–20 mg or rosuvastatin 5–10 mg) plus ezetimibe (n = 922) or high-intensity statins (atorvastatin 40–80 mg or rosuvastatin 20 mg; n = 19,148). The primary outcome was a composite of cardiovascular mortality, hospitalization for myocardial infarction (MI), hospitalization for stroke, or revascularization. Results: At 12 months, the incidence rates of the primary outcome were 138.0 vs. 154.0 per 1000 person-years in the moderate-intensity stains plus ezetimibe and the high-intensity statins group, respectively. The fully adjusted hazard ratio [HR] for the primary outcome was 1.11 (95% confidence interval [CI] 0.86–1.42; p = 0.43). The multivariable-adjusted HR for a composite of cardiovascular mortality, hospitalization for MI, or hospitalization for stroke was 1.05 (95% CI 0.74–1.47; p = 0.80). During follow-up, the proportion of patients maintaining their initial lipid-lowering therapy was significantly higher in the moderate-intensity statins plus ezetimibe group than in the high-intensity statins group. Conclusions: Patients undergoing a coronary revascularization procedure who received moderate-intensity statins plus ezetimibe showed similar rates of major adverse cardiovascular events as patients who received high-intensity statins.Multivariate longitudinal data for survival analysis of cardiovascular event prediction in young adults: insights from a comparative explainable study
AbstractNguyen, H. T., Vasconcellos, H. D., Keck, K., Reis, J. P., Lewis, C. E., Sidney, S., Lloyd-Jones, D. M., Schreiner, P. J., Guallar, E., Wu, C. O., Lima, J. A., & Ambale-Venkatesh, B. (n.d.).Publication year
2023Journal title
BMC Medical Research MethodologyVolume
23Issue
1AbstractBackground: Multivariate longitudinal data are under-utilized for survival analysis compared to cross-sectional data (CS - data collected once across cohort). Particularly in cardiovascular risk prediction, despite available methods of longitudinal data analysis, the value of longitudinal information has not been established in terms of improved predictive accuracy and clinical applicability. Methods: We investigated the value of longitudinal data over and above the use of cross-sectional data via 6 distinct modeling strategies from statistics, machine learning, and deep learning that incorporate repeated measures for survival analysis of the time-to-cardiovascular event in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. We then examined and compared the use of model-specific interpretability methods (Random Survival Forest Variable Importance) and model-agnostic methods (SHapley Additive exPlanation (SHAP) and Temporal Importance Model Explanation (TIME)) in cardiovascular risk prediction using the top-performing models. Results: In a cohort of 3539 participants, longitudinal information from 35 variables that were repeatedly collected in 6 exam visits over 15 years improved subsequent long-term (17 years after) risk prediction by up to 8.3% in C-index compared to using baseline data (0.78 vs. 0.72), and up to approximately 4% compared to using the last observed CS data (0.75). Time-varying AUC was also higher in models using longitudinal data (0.86–0.87 at 5 years, 0.79–0.81 at 10 years) than using baseline or last observed CS data (0.80–0.86 at 5 years, 0.73–0.77 at 10 years). Comparative model interpretability analysis revealed the impact of longitudinal variables on model prediction on both the individual and global scales among different modeling strategies, as well as identifying the best time windows and best timing within that window for event prediction. The best strategy to incorporate longitudinal data for accuracy was time series massive feature extraction, and the easiest interpretable strategy was trajectory clustering. Conclusion: Our analysis demonstrates the added value of longitudinal data in predictive accuracy and epidemiological utility in cardiovascular risk survival analysis in young adults via a unified, scalable framework that compares model performance and explainability. The framework can be extended to a larger number of variables and other longitudinal modeling methods. Trial registration: ClinicalTrials.gov Identifier: NCT00005130, Registration Date: 26/05/2000.Nonalcoholic Fatty Liver Disease Without Metabolic-associated Fatty Liver Disease and the Risk of Metabolic Syndrome
AbstractSinn, D. H., Kang, D., Choi, S. C., Hong, Y. S., Zhao, D., Guallar, E., Park, Y., Cho, J., & Gwak, G. Y. (n.d.).Publication year
2023Journal title
Clinical Gastroenterology and HepatologyVolume
21Issue
7Page(s)
1873-1880.e1AbstractBackground & Aims: Metabolic (dysfunction)-associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD). Some people fulfill diagnostic criteria of NAFLD but not MAFLD (NAFLD without MAFLD), but the clinical implications of NAFLD in these subjects is unknown. Methods: We followed cohort of 12,197 men and women 20 years of age or older without metabolic dysfunction (defined by MAFLD criteria), heavy alcohol use, chronic viral hepatitis, liver cirrhosis, or malignancy for their risk of incident metabolic syndrome defined by Adult Treatment Panel III criteria. Results: By design, none of the study participants had MAFLD at baseline. The prevalence of NAFLD among participants without metabolic dysfunction meeting MAFLD criteria and without significant alcohol intake was 7.6%. During 74,508 person-years of follow-up, 2179 participants developed metabolic syndrome. The fully adjusted hazard ratio for metabolic syndrome comparing participants with NAFLD to those without it was 1.61 (95% confidence interval, 1.42–1.83). The increased risk of incident metabolic syndrome associated with NAFLD persisted for all studied subgroups, and the association was stronger for those with increased waist circumference (P for interaction = .029) and those without elevated triglycerides levels (P for interaction = .047). Conclusion: In this large cohort, participants with NAFLD without MAFLD were at higher risk of developing metabolic syndrome compared to participants with no NAFLD and no MAFLD. Using MAFLD criteria may miss opportunities for early intervention in these subjects.Obesity paradox in patients with non-small cell lung cancer undergoing immune checkpoint inhibitor therapy
AbstractLee, J. H., Kang, D., Ahn, J. S., Guallar, E., Cho, J., & Lee, H. Y. (n.d.).Publication year
2023Journal title
Journal of Cachexia, Sarcopenia and MuscleVolume
14Issue
6Page(s)
2898-2907AbstractBackground: The obesity paradox in patients with advanced non-small cell lung cancer receiving immune checkpoint inhibitor therapy has been observed, but its underlying mechanism is not fully understood. We aimed to investigate whether body composition affects the prognostic impact of obesity, as determined by body mass index (BMI), on survival. Methods: This retrospective study evaluated the data collected from Asian patients who were treated with immune checkpoint inhibitors for advanced non-small cell lung cancer between October 2015 and October 2021. We used abdominal cross-sectional imaging to calculate the skeletal muscle and visceral fat indices (cm2/m2) by dividing the cross-sectional areas of the skeletal muscle and visceral fat by the height squared. Cox proportional-hazards regression was performed to determine the correlation between BMI according to the Asia-Pacific classification, body composition metrics and overall survival. Results: We analysed the data of 820 patients (630 men and 190 women, with a mean age of 64.3 years [standard deviation: 10.4 years]) and observed 572 (69.8%) deaths with the 1-year mortality rate of 0.58 (95% confidence interval, 0.55–0.62). Obese BMI was associated with longer overall survival, independent of clinical covariates (hazard ratio, 0.64; 95% confidence interval: 0.52–0.80). The prognostic value of obese BMI remained after additional adjustments for skeletal muscle index (hazard ratio, 0.68; 95% confidence interval, 0.53–0.87) or visceral fat index (hazard ratio, 0.54; 95% confidence interval: 0.41–0.70). No association was observed between sex and the impact of BMI on overall survival (P-value for interaction >0.05). Conclusions: In Asian patients with advanced non-small cell lung cancer who received immune checkpoint inhibitors, obese BMI was associated with favourable overall survival independent of skeletal muscle or visceral fat mass.Oxidative Stress and Cardiovascular Risk Factors: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
AbstractHeravi, A. S., Zhao, D., Michos, E. D., Doria De Vasconcellos, H., Ambale-Venkatesh, B., Lloyd-Jones, D., Schreiner, P. J., Reis, J. P., Shikany, J. M., Lewis, C. E., Ndumele, C. E., Guallar, E., Ouyang, P., Hoogeveen, R. C., Lima, J. A., Post, W. S., & Vaidya, D. (n.d.).Publication year
2023Journal title
AntioxidantsVolume
12Issue
3AbstractIntroduction—Oxidative stress is linked to cardiovascular diseases (CVD) and is suggested to vary by sex. However, few population-level studies have explored these associations and the majority comprise populations with advanced CVD. We assessed urinary isoprostane concentrations, a standard measure of oxidative stress, in a relatively young and healthy cohort, hypothesizing that higher oxidative stress is associated with an adverse cardiometabolic profile and female sex. Methods—Oxidative stress was measured in 475 women and 266 men, aged 48–55 years, from the Coronary Artery Risk Development in Young Adults (CARDIA) study using urinary 8-isoprostane (IsoP) and 2,3-dinor-8-isoprostane (IsoP-M). Multivariable-adjusted regression was used to evaluate cross-sectional associations. As secondary analysis, previously measured plasma F2-isoprostanes (plasma IsoP) from another CARDIA subset was similarly analyzed. Results—Mean (SD) ages for men and women were 52.1(2.3) and 52.2(2.2) years, respectively (p = 0.46), and 39% of the participants self-identified as Black (vs. White). Before adjustments, female sex was associated with higher median urinary IsoP (880 vs. 704 ng/g creatinine in men; p < 0.01) and IsoP m (1675 vs. 1284 ng/g creatinine in men; p < 0.01). Higher body mass index (BMI), high-density cholesterol (HDL-C), and triglycerides, current smoking, and less physical activity were associated with higher oxidative stress. Diabetes was not associated with urinary IsoP but was associated with lower IsoP m and plasma IsoP. Higher serum creatinine showed diverging associations with higher plasma and lower urinary isoprostane concentrations. Conclusions—Different isoprostane entities exhibit varying association patterns with CVD risk factors, and therefore are complementary, rather than interchangeable, in assessment of oxidative stress. Still, consistently higher isoprostanes among women, smokers, less active persons, and those with higher BMI and plasma triglycerides could reflect higher oxidative stress among these groups. While urinary isoprostanes are indexed to urinary creatinine due to variations in concentration, caution should be exercised when comparing groups with differing serum creatinine.Regression of nonalcoholic fatty liver disease is associated with reduced risk of incident diabetes: A longitudinal cohort study
AbstractSinn, D. H., Kang, D., Guallar, E., Choi, S. C., Hong, Y. S., Park, Y., Cho, J., & Gwak, G. Y. (n.d.).Publication year
2023Journal title
PloS oneVolume
18Issue
7AbstractObjective Non-alcoholic fatty liver disease (NAFLD) is potentially reversible. However, whether improvement of NAFLD leads to clinical benefits remains uncertain. We investigated the association between regression of NAFLD and the risk of incident diabetes in a longitudinal way. Methods A cohort of 11,260 adults who had NAFLD at in an initial exam, had the second evaluation for NAFLD status at 1~2 years from an initial exam were followed up for incident diabetes from 2001 and 2016. NAFLD was diagnosed with abdominal ultrasound. Results At baseline, NAFLD was regressed in 2,559 participants (22.7%). During 51,388 person-years of follow-up (median 4 years), 1,768 participants developed diabetes. The fully adjusted hazard ratio (HR) for incident diabetes in participants with regressed NAFLD compared to those with persistent NAFLD was 0.81 [95% confidence interval (CI) 0.72–0.92]. When assessed by NAFLD severity, among participants with a low NAFLD fibrosis score (NFS) (< -1.455), participants with regressed NAFLD had a lower risk of incident diabetes than those with persistent NAFLD (HR 0.77, 95% CI 0.68–0.88). However, in participants with an intermediate to high NFS (≥ -1.455), the risk of incident diabetes was not different between NAFLD regression and persistence groups (HR 1.12, 95% CI 0.82–1.51). Conclusions Regression of NAFLD was associated with decreased risk of incident diabetes compared to persistent NAFLD. However, the benefit was evident only for NAFLD patients with low NFS. This suggests that early intervention for NAFLD, before advanced fibrosis is present, may maximize the metabolic benefit from NAFLD regression.Reply
Sinn, D. H., Kang, D., Guallar, E., Cho, J., & Gwak, G. Y. (n.d.). In Clinical Gastroenterology and Hepatology (1–).Publication year
2023Volume
21Issue
9Page(s)
2435-2436Seeing the Positive in Negative Studies
Guallar, E., Goodman, S. N., Localio, A. R., Stephens-Shields, A. J., & Laine, C. (n.d.).Publication year
2023Journal title
Annals of internal medicineVolume
176Issue
4Page(s)
561-563Validation of the IASLC Residual Tumor Classification in Patients with Stage III-N2 Non-Small Cell Lung Cancer Undergoing Neoadjuvant Chemoradiotherapy Followed by Surgery
AbstractLee, J., Lee, J., Hong, Y. S., Lee, G., Kang, D., Yun, J., Jeon, Y. J., Shin, S., Cho, J. H., Choi, Y. S., Kim, J., Zo, J. I., Shim, Y. M., Guallar, E., Cho, J., & Kim, H. K. (n.d.).Publication year
2023Journal title
Annals of SurgeryVolume
277Issue
6Page(s)
E1355-E1363AbstractObjective: The aim of this study was to validate the International Association for the Study of Lung Cancer (IASLC) residual tumor classification in patients with stage III-N2 non-small cell lung cancer (NSCLC) undergoing neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by surgery. Background: As adequate nodal assessment is crucial for determining prognosis in patients with clinical N2 NSCLC undergoing nCCRT followed by surgery, the new classification may have better prognostic implications. Methods: Using a registry for thoracic cancer surgery at a tertiary hospital in Seoul, Korea, between 2003 and 2019, we analyzed 910 patients with stage III-N2 NSCLC who underwent nCCRT followed by surgery. We classified resections using IASLC criteria: complete (R0), uncertain (R[un]), and incomplete resection (R1/R2). Recurrence and mortality were compared using adjusted subdistribution hazard model and Cox-proportional hazards model, respectively. Results: Of the 96.3% (n = 876) patients who were R0 by Union for International Cancer Control (UICC) criteria, 34.5% (n = 3O2) remained R0 by IASLC criteria and 37.6% (n = 329) and 28% (n = 245) migrated to R(un) and R1, respectively. Most of the migration from UICC-R0 to lASLC-R(un) and IASLC-R1/R2 occurred due to inadequate nodal assessment (85.5%) and extracapsular nodal extension (77.6%), respectively. Compared to R0, the adjusted hazard ratios in R(un) and R1/R2 were 1.20 (95% confidence interval, 0.94-1.52), 1.50 (1.17-1.52) (P fortrend =.001) for recurrence and 1.18 (0.93-1.51) and 1.51 (1.17-1.96) for death (P for trend =.002). Conclusions: The IASLC R classification has prognostic relevance in patients with stage III-N2 NSCLC undergoing nCCRT followed by surgery. The IASLC classification will improve the thoroughness of intraoperative nodal assessment and the completeness of resection.Vasomotor and other menopause symptoms and the prevalence of ideal cardiovascular health metrics among premenopausal stage women
AbstractChoi, H. R., Chang, Y., Kim, Y., Cho, Y., Kwon, M. J., Kang, J., Kwon, R., Lim, G. Y., Kim, K. H., Kim, H., Hong, Y. S., Park, J., Zhao, D., Cho, J., Guallar, E., Park, H. Y., & Ryu, S. (n.d.).Publication year
2023Journal title
MenopauseVolume
30Issue
7Page(s)
750-757AbstractObjective We examined the association between menopause symptoms and the prevalence of ideal cardiovascular health (CVH) metrics among premenopausal women. Methods This cross-sectional study comprised 4,611 premenopausal women aged 42 to 52 years. Data for CVH metrics were collected during health screening examinations. Menopause symptoms were measured using the Korean version of the Menopause-Specific Quality of Life questionnaire. For vasomotor, psychosocial, physical, and sexual symptoms, participants were divided into absent or symptomatic groups, further divided into tertiles (range, 0-7; 7 being the most bothersome). Ideal CVH metrics were defined according to the American Heart Association Life Simple 7 metrics, except dietary component. Cardiovascular health metrics were scored from 0 (unhealthy) to 6 (healthy) and classified as poor (0-2), intermediate (3-4), and ideal (5-6). Multinomial logistic regression models were used to estimate the prevalence ratios for intermediate and poor CVH metrics using ideal CVH as the reference. Results The overall and 4 menopause-specific quality of life domain scores were significantly associated with poorer CVH metrics scores in a dose-response manner (P < 0.05). After adjusting for age, parity, education level, anti-Mullerian hormone levels, and alcohol intake, women with the most bothersome degree for vasomotor, psychosocial, physical, and sexual symptoms had significantly higher prevalence of poor CVH metrics, with corresponding prevalence ratios (95% confidence interval) of 2.90 (1.95-4.31), 2.07 (1.36-3.15), 3.01 (1.19-7.65), and 1.66 (1.15-2.39), respectively, compared with those without each vasomotor, psychosocial, physical, and sexual symptom. Conclusions Premenopausal stage women with either vasomotor or nonvasomotor menopausal symptoms have significantly higher prevalence of poor CVH metrics, compared with those without any menopausal symptoms.Whole-exome sequencing in 415,422 individuals identifies rare variants associated with mitochondrial DNA copy number
AbstractPillalamarri, V., Shi, W., Say, C., Yang, S., Lane, J., Guallar, E., Pankratz, N., & Arking, D. E. (n.d.).Publication year
2023Journal title
Human Genetics and Genomics AdvancesVolume
4Issue
1AbstractInter-individual variation in the number of copies of the mitochondrial genome, called mitochondrial DNA copy number (mtDNA-CN), reflects mitochondrial function and has been associated with various aging-related diseases. We examined 415,422 exomes of self-reported White ancestry individuals from the UK Biobank and tested the impact of rare variants, at the level of single variants and through aggregate variant-set tests, on mtDNA-CN. A survey across nine variant sets tested enrichment of putatively causal variants and identified 14 genes at experiment-wide significance and three genes at marginal significance. These included associations at known mtDNA depletion syndrome genes (mtDNA helicase TWNK, p = 1.1 × 10−30; mitochondrial transcription factor TFAM, p = 4.3 × 10−15; mtDNA maintenance exonuclease MGME1, p = 2.0 × 10−6) and the V617F dominant gain-of-function mutation in the tyrosine kinase JAK2 (p = 2.7 × 10−17), associated with myeloproliferative disease. Novel genes included the ATP-dependent protease CLPX (p = 8.4 × 10−9), involved in mitochondrial proteome quality, and the mitochondrial adenylate kinase AK2 (p = 4.7 × 10−8), involved in hematopoiesis. The most significant association was a missense variant in SAMHD1 (p = 4.2 × 10−28), found on a rare, 1.2-Mb shared ancestral haplotype on chromosome 20. SAMHD1 encodes a cytoplasmic host restriction factor involved in viral defense response and the mitochondrial nucleotide salvage pathway, and is associated with Aicardi-Goutières syndrome 5, a childhood encephalopathy and chronic inflammatory response disorder. Rare variants were enriched in Mendelian mtDNA depletion syndrome loci, and these variants implicated core processes in mtDNA replication, nucleoid structure formation, and maintenance. These data indicate that strong-effect mutations from the nuclear genome contribute to the genetic architecture of mtDNA-CN.A metabolomics approach identified toxins associated with uremic symptoms in advanced chronic kidney disease
AbstractHu, J. R., Myint, L., Levey, A. S., Coresh, J., Inker, L. A., Grams, M. E., Guallar, E., Hansen, K. D., Rhee, E. P., & Shafi, T. (n.d.).Publication year
2022Journal title
Kidney InternationalVolume
101Issue
2Page(s)
369-378AbstractUremic symptoms are common in patients with advanced chronic kidney disease, but the toxins that cause these symptoms are unknown. To evaluate this, we performed a cross-sectional study of the 12 month post-randomization follow-up visit of Modification of Diet in Renal Disease (MDRD) participants reporting uremic symptoms who also had available stored serum. We quantified 1,163 metabolites by liquid chromatography-tandem mass spectrometry. For each uremic symptom, we calculated a score as the severity multiplied by the number of days the symptom was experienced. We analyzed the associations of the individual symptom scores with metabolites using linear models with empirical Bayesian inference, adjusted for multiple comparisons. Among 695 participants, the mean measured glomerular filtration rate (mGFR) was 28 mL/min/1.73 m2. Uremic symptoms were more common in the subgroup of 214 patients with an mGFR under 20 mL/min/1.73 m2 (mGFR under 20 subgroup) than in the full group. For all metabolites with significant associations, the direction of the association was concordant in the full group and the subgroup. For gastrointestinal symptoms (bad taste, loss of appetite, nausea, and vomiting), eleven metabolites were associated with symptoms. For neurologic symptoms (decreased alertness, falling asleep during the day, forgetfulness, lack of pep and energy, and tiring easily/weakness), seven metabolites were associated with symptoms. Associations were consistent across sensitivity analyses. Thus, our proof-of-principle study demonstrates the potential for metabolomics to understand metabolic pathways associated with uremic symptoms. Larger, prospective studies with external validation are needed.Adherence to Diet and Meal Timing in a Randomized Controlled Feeding Study of Time‐Restricted Feeding
AbstractWu, B., White, K., Maw, M. T. T., Charleston, J., Zhao, D., Guallar, E., Appel, L. J., Clark, J. M., Maruthur, N. M., & Pilla, S. J. (n.d.).Publication year
2022Journal title
NutrientsVolume
14Issue
11AbstractAdherence is critical in feeding studies to determine the efficacy of dietary interventions. This time‐restricted intake of meals (TRIM) investigation was a controlled feeding study that randomized 41 participants to follow 12 weeks of time‐restricted feeding (TRF) or a usual feeding pattern (UFP). Adherence was optimized through careful screening and participant orientation, flexibility in beverages and seasonings, and frequent contact between participants and staff. Adherence was measured daily using a self‐administered diary form. We calculated the percentage of participant‐days with perfect adherence to meal timing (ate all meals within their designated time window) and to food consumption (ate all study food and no non‐study food). Adherence was compared between study arms, days of the week, and weeks of the study period using generalized estimating equations (GEE) regression. There was perfect adherence to meal timing on 87% of participant‐days and to food consumption on 94% of participant-days, with no significant difference by arm. In UFP, but not TRF, participants had lower adherence to meal timing over the weekend (p‐value = 0.002) and during the first two weeks of intervention (p‐value = 0.03). A controlled feeding study randomizing free‐living individuals to different meal timings achieved a high degree of adherence to meal timing and food consumption, utilizing multiple strategies.Alcohol Consumption Patterns and Risk of Early-Onset Vasomotor Symptoms in Premenopausal Women
AbstractKwon, R., Chang, Y., Kim, Y., Cho, Y., Choi, H. R., Lim, G. Y., Kang, J., Kim, K. H., Kim, H., Hong, Y. S., Park, J., Zhao, D., Rampal, S., Cho, J., Guallar, E., Park, H. Y., & Ryu, S. (n.d.).Publication year
2022Journal title
NutrientsVolume
14Issue
11AbstractThe role of alcohol consumption in the risk of vasomotor symptoms (VMS), the most cardinal climacteric symptoms, is not well established. We examined their relationship with early-onset VMS among premenopausal women. Moderately-to-severely bothersome VMS, the primary outcome, was assessed using the Korean version of the Menopause-Specific Quality of Life questionnaire. The alcohol consumption categories included lifetime abstainer, former drinker, or current drinker, categorized as light, moderate, heavy, and very heavy. Compared with the lifetime-abstinence (reference), the multivariable-adjusted odds ratio (95% CIs) for prevalent VMS in alcohol consumption of <10, 10–19, 20–39, and ≥40 g/day were 1.42 (1.02–1.99), 1.99 (1.27–3.12), 2.06 (1.19–3.57), and 3.52 (1.72–7.20), respectively (p trend <0.01). Compared with the lifetime-abstinence, the multivariable-adjusted hazard ratios (95% CIs) for incident bothersome VMS among average alcohol consumption of <10, 10–19, 20–39, and ≥40 g/day were 1.10 (0.85–1.41), 1.03 (0.70–1.51), 1.72 (1.06–2.78), and 2.22 (1.16–4.23), respectively (p trend = 0.02). Increased alcohol consumption positively and consistently showed a relationship with increased risk of both prevalent and incident early-onset VMS. Refraining from alcohol consumption may help prevent bothersome VMS in premenopausal women.Assessing the Accuracy of Estimated Lipoprotein(a) Cholesterol and Lipoprotein(a)-Free Low-Density Lipoprotein Cholesterol
AbstractZheng, W., Chilazi, M., Park, J., Sathiyakumar, V., Donato, L. J., Meeusen, J. W., Lazo, M., Guallar, E., Kulkarni, K. R., Jaffe, A. S., Santos, R. D., Toth, P. P., Jones, S. R., & Martin, S. S. (n.d.).Publication year
2022Journal title
Journal of the American Heart AssociationVolume
11Issue
2AbstractBACKGROUND: Accurate measurement of the cholesterol within lipoprotein(a) (Lp[a]-C) and its contribution to low-density lipo-protein cholesterol (LDL-C) has important implications for risk assessment, diagnosis, and treatment of atherosclerotic cardiovascular disease, as well as in familial hypercholesterolemia. A method for estimating Lp(a)-C from particle number using fixed conversion factors has been proposed (Lp[a]-C from particle number divided by 2.4 for Lp(a) mass, multiplied by 30% for Lp[a]-C). The accuracy of this method, which theoretically can isolate “Lp(a)-free LDL-C,” has not been validated. METHODS AND RESULTS: In 177 875 patients from the VLDbL (Very Large Database of Lipids), we compared estimated Lp(a)-C and Lp(a)-free LDL-C with measured values and quantified absolute and percent error. We compared findings with an analo-gous data set from the Mayo Clinic Laboratory. Error in estimated Lp(a)-C and Lp(a)-free LDL-C increased with higher Lp(a)-C values. Median error for estimated Lp(a)-C <10 mg/dL was −1.9 mg/dL (interquartile range, −4.0 to 0.2); this error increased lin-early, overestimating by +30.8 mg/dL (interquartile range, 26.1– 36.5) for estimated Lp(a)-C ≥50 mg/dL. This error relationship persisted after stratification by overall high-density lipoprotein cholesterol and high-density lipoprotein cholesterol subtypes. Similar findings were observed in the Mayo cohort. Absolute error for Lp(a)-free LDL-C was +2.4 (interquartile range, −0.6 to 5.3) for Lp(a)-C<10 mg/dL and −31.8 (interquartile range, −37.8 to −26.5) mg/dL for Lp(a)-C≥50 mg/dL. CONCLUSIONS: Lp(a)-C estimations using fixed conversion factors overestimated Lp(a)-C and subsequently underestimated Lp(a)-free LDL-C, especially at clinically relevant Lp(a) values. Application of inaccurate Lp(a)-C estimations to correct LDL-C may lead to undertreatment of high-risk patients.Association Between Retinopathy of Prematurity in Very-Low-Birth-Weight Infants and Neurodevelopmental Impairment
AbstractHan, G., Lim, D. H., Kang, D., Cho, J., Guallar, E., Chang, Y. S., Chung, T. Y., Kim, S. J., & Park, W. S. (n.d.).Publication year
2022Journal title
American Journal of OphthalmologyVolume
244Page(s)
205-215AbstractPurpose: To evaluate the impact of retinopathy of prematurity (ROP) severity and the treatment of very-low-birth-weight infants (VLBWIs) on neurodevelopmental impairment in early childhood. Design: Prospective cohort study. Method: This was a prospective cohort study. The data were obtained from the Korean Neonatal Network (KNN), a nationwide registry for VLBWIs. Infants who were born from 2013 to 2015 and underwent ROP evaluation at birth and neurodevelopmental examinations at corrected ages of 18 to 24 months were included in the study. Infants with a history of meningitis or severe congenital anomalies were excluded. The VLBWI patients were grouped into no ROP, no treatment-requiring ROP (non−TR-ROP), and treatment-requiring ROP (TR-ROP) groups. Neurodevelopmental impairment was defined as participants who had at least 1 developmental problem according to the Bayley Scales of Infant and Toddler Development−2nd Edition (Bayley-II; <70), Bayley Scales of Infant and Toddler Development−3rd Edition (Bayley-III; <70), and Korean Developmental Screening Test (K-DST) tests (below −1 SD), and the Korean Ages and Stages Questionnaire (K-ASQ) (below the threshold) and Gross Motor Function Classification System (GMFCS; at level 2 or above). Multivariable logistic regression analysis was performed to evaluate the association between ROP and neurodevelopmental impairment. Result: Among 3132 infants, 1093 (34.9%) had ROP. Among the ROP infants, 644 were not treated for ROP (non-TR-ROP group) and 449 received ROP treatments (TR-ROP group). The patients in the TR-ROP group had an increased risk of developing neurodevelopmental problems compared to those in the no ROP group (odds ratio [OR] = 1.72, 95% CI = 1.33-2.21). The TR-ROP group had a higher risk of all 3 types of neurodevelopmental problems: mental (OR = 1.62, 95% CI = 1.25-2.09), social (OR = 1.62, 95% CI = 1.12-2.09), and motor (OR = 1.69, 95% CI = 1.31-2.18). The risk of neurodevelopmental problems in patients treated with laser therapy did not differ from that in patients treated with anti−vascular endothelial growth factor (anti-VEGF) therapy (OR = 1.17, 95% CI = 0.73-1.88). Conclusion: ROP was independently associated with neurodevelopmental impairment in early childhood. The type of ROP treatment (anti-VEGF or laser treatment) did not affect neurodevelopmental impairment in patients in the TR-ROP group.Associations between aflatoxin B1-albumin adduct levels with metabolic conditions in Guatemala: A cross-sectional study
AbstractAlvarez, C. S., Rivera-Andrade, A., Kroker-Lobos, M. F., Florio, A. A., Smith, J. W., Egner, P. A., Freedman, N. D., Lazo, M., Guallar, E., Dean, M., Graubard, B. I., Ramírez-Zea, M., McGlynn, K. A., & Groopman, J. D. (n.d.).Publication year
2022Journal title
Health Science ReportsVolume
5Issue
1AbstractBackground and Aims: Metabolic conditions such as obesity, type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) are highly prevalent in Guatemala and increase the risk for a number of disorders, including hepatocellular carcinoma (HCC). Aflatoxin B1 (AFB1) levels are also notably elevated in the population and are known to be associated with HCC risk. Whether AFB1 also contributes to the high prevalence of the metabolic disorders has not been previously examined. Therefore, the purpose of this study was to assess the association between AFB1 and the metabolic conditions. Methods: Four-hundred twenty-three individuals were included in the study, in which AFB1-albumin adduct levels were measured in sera. Metabolic conditions included diabetes, obesity, central obesity, metabolic syndrome, and NAFLD. Crude and adjusted prevalence odds ratios (PORs) and 95% confidence intervals (95% CI) were estimated for the associations between the metabolic conditions and AFB1-albumin adduct levels categorized into quartiles. Results: The study found a significant association between AFB1-albumin adduct levels and diabetes (Q4 vs Q1 POR = 3.74, 95%CI: 1.71-8.19; P-trend.003). No associations were observed between AFB1-albumin adduct levels and the other conditions. Conclusions: As diabetes is the metabolic condition most consistently linked to HCC, the possible association between AFB1 exposure and diabetes may be of public health importance. Further studies are warranted to replicate the findings and examine potential mechanisms.Circulating bile acid concentrations and non-alcoholic fatty liver disease in Guatemala
AbstractRivera-Andrade, A., Petrick, J. L., Alvarez, C. S., Graubard, B. I., Florio, A. A., Kroker-Lobos, M. F., Parisi, D., Freedman, N. D., Lazo, M., Guallar, E., Groopman, J. D., Ramirez-Zea, M., & McGlynn, K. A. (n.d.).Publication year
2022Journal title
Alimentary Pharmacology and TherapeuticsVolume
56Issue
2Page(s)
321-329AbstractBackground: Non-alcoholic fatty liver disease (NAFLD) is a major liver disease worldwide. Bile acid dysregulation may be a key feature in its pathogenesis and progression. Aims: To characterise the relationship between bile acid levels and NAFLD at the population level. Methods: We conducted a cross-sectional study in Guatemala in 2016 to examine the prevalence of NAFLD. Participants (n = 415) completed questionnaires, donated blood samples and had a brief medical exam. NAFLD was determined by calculation of the fatty liver index. The levels of 15 circulating bile acids were determined by LC–MS/MS. Adjusted prevalence odds ratios (PORadj) and 95% CI were calculated to examine the relationships between bile acid levels (in tertiles) and NAFLD. Results: Persons with NAFLD had significantly higher levels of the conjugated primary bile acids glycocholic acid (GCA) (PORadj T3 vs T1 = 1.85), taurocholic acid (TCA) (PORadj T3 vs T1 = 2.45) and taurochenodeoxycholic acid (TCDCA) (PORadj T3 vs T1 = 2.10), as well as significantly higher levels the unconjugated secondary bile acid, deoxycholic acid (DCA) (PORadj T3 vs T1 = 1.78) and its conjugated form, taurodeoxycholic acid (TDCA) (PORadj T3 vs T1 = 1.81). Conclusions: The bile acid levels of persons with and without NAFLD differed significantly. Among persons with NAFLD, higher levels of the conjugated forms of CA (i.e. GCA, TCA) and the secondary bile acids that derive from CA (i.e. DCA, TDCA) may indicate there is hepatic overproduction of CA, which may affect the liver via aberrant signalling mediated by the bile acids.